The principal investigator has previously studied the immunosuppressive effects of hamster serum fraction enriched for alpha2 macroglobulin (A2M). In these studies there was a differential inhibition of stimulation of lymphocytes by B-cell mitogens. The inhibitory fraction (A2M) also possessed protease inhibitor activity. The purpose of this study is to extend the biochemical purification A2M and analyze its biological role as a regulator of cellular proliferation. Initial experiments involved biochemical isolation and characterization of A2M from hamster serum and characterization of a monospecific antisera generated in rabbits. The following biological characterization of A2M from serum will be investigated: 1) The role of A2M in proliferation will be analyzed by adding A2M to in-vitro primary antibody forming cell cultures; 2) cells bearing surface A2M will be localized and distribution patterns followed by utilizing immunofluorescent antibody techniques; 3) serum A2M levels of normal and immunized animals will be quantitated by rocket immunoelectrophoresis. Once biological characteristics are determined for normal animals and normal cells the investigation will be extended to study the same qualities in tumor bearing animals and in-vitro transformed cell lines. The results obtained from the proposed research will provide information on how protease/protease inhibitor systems may aid in regulation of cellular proliferation and/or differentiation and more specifically how the interaction of tumor cells and the immune system may result in immunosuppression through these molecules.